Amino acids bind to phase-separating proteins and modulate biomolecular condensate stability and dynamics

Xufeng Xu (), Merlijn H. I. Haren, Iris B. A. Smokers, Brent S. Visser, Paul B. White, Robert S. Jansen and Evan Spruijt ()
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Xufeng Xu: Radboud University
Merlijn H. I. Haren: Radboud University
Iris B. A. Smokers: Radboud University
Brent S. Visser: Radboud University
Paul B. White: Radboud University
Robert S. Jansen: Radboud University
Evan Spruijt: Radboud University

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Biomolecular condensates (BCs) are ubiquitous compartments that regulate key functions in cells. BCs are surrounded by a complex intracellular environment, of which amino acids (AAs) are prominent components. However, it is unclear how AAs interact with condensate components and influence the material properties of condensates. Here, we demonstrate that phase separation is suppressed with glycine by using model heterotypic condensates composed of nucleophosmin 1 and ribosomal ribonucleic acid. The condensate density decreases, and the dynamics within the condensate increase. We find that glycine weakly binds to amide groups in the protein backbone and aromatic groups in the side chains, weakening the backbone-backbone interactions between neutral and charged disordered proteins while strengthening the interactions between aromatic stickers. This leads to different modulations of the phase behaviour in condensates formed by π/cation-π interactions and charge complexation. We further show that a modulation effect on BCs is observed for other proteinogenic AAs and can be transferred to short homopeptides. These insights offer strategies to modulate the dynamic properties of BCs in vivo.

Date: 2025
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DOI: 10.1038/s41467-025-63755-x

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